College of Arts and Sciences, SUNY Polytechnic Institute, Utica, New York, United States of America.
Metabolomics Core Resource Laboratory, New York University Langone Heath, New York, New York, United States of America.
PLoS One. 2020 Feb 13;15(2):e0229103. doi: 10.1371/journal.pone.0229103. eCollection 2020.
Chemical modifications that regulate protein expression at the translational level are emerging as vital components of the cellular stress response. Transfer RNAs (tRNAs) are significant targets for methyl-based modifications, which are catalyzed by tRNA methyltransferases (Trms). Here, Saccharomyces cerevisiae served as a model eukaryote system to investigate the role of 2'-O-ribose tRNA methylation in the cell's response to oxidative stress. Using 2'-O-ribose deletion mutants for trms 3, 7, 13, and 44, in acute and chronic exposure settings, we demonstrate a broad cell sensitivity to oxidative stress-inducing toxicants (i.e., hydrogen peroxide, rotenone, and acetic acid). A global analysis of hydrogen peroxide-induced tRNA modifications shows a complex profile of decreased, or undetectable, 2'-O-ribose modification events in 2'-O-ribose trm mutant strains, providing a critical link between this type of modification event and Trm status post-exposure. Based on the pronounced oxidative stress sensitivity observed for trm7 mutants, we used a bioinformatic tool to identify transcripts as candidates for regulation by Trm7-catalyzed modifications (i.e., enriched in UUC codons decoded by tRNAPheGmAA). This screen identified transcripts linked to diverse biological processes that promote cellular recovery after oxidative stress exposure, including DNA repair, chromatin remodeling, and nutrient acquisition (i.e., CRT10, HIR3, HXT2, and GNP1); moreover, these mutants were also oxidative stress-sensitive. Together, these results solidify a role for TRM3, 7, 13, and 44, in the cellular response to oxidative stress, and implicate 2'-O-ribose tRNA modification as an epitranscriptomic strategy for oxidative stress recovery.
在翻译为简体中文时，我会尽量保留原文的语序和语法结构，以确保译文的流畅性和自然度。
化学修饰可以在翻译水平上调节蛋白质表达，它们正成为细胞应激反应的重要组成部分。转移 RNA（tRNA）是基于甲基的修饰的重要靶标，这些修饰由 tRNA 甲基转移酶（Trms）催化。在这里，酿酒酵母被用作模式真核生物系统，以研究 2'-O-核糖 tRNA 甲基化在细胞对氧化应激的反应中的作用。在急性和慢性暴露条件下，使用 trms3、7、13 和 44 的 2'-O-核糖缺失突变体，我们证明了细胞对氧化应激诱导的毒物（即过氧化氢、鱼藤酮和乙酸）具有广泛的敏感性。对过氧化氢诱导的 tRNA 修饰的全局分析显示，在 2'-O-核糖 trm 突变菌株中，2'-O-核糖修饰事件的减少或无法检测到，呈现出复杂的谱，这为这种修饰事件与暴露后 Trm 状态之间提供了关键联系。基于 trm7 突变体观察到的明显氧化应激敏感性，我们使用生物信息学工具来鉴定转录本作为 Trm7 催化修饰调节的候选物（即富含由 tRNAPheGmAA 解码的 UUC 密码子）。该筛选确定了与各种生物过程相关的转录本，这些过程可促进细胞在氧化应激暴露后恢复，包括 DNA 修复、染色质重塑和营养物质获取（即 CRT10、HIR3、HXT2 和 GNP1）；此外，这些突变体也对氧化应激敏感。总之，这些结果确定了 TRM3、7、13 和 44 在细胞对氧化应激的反应中的作用，并暗示 2'-O-核糖 tRNA 修饰是氧化应激恢复的一种表观转录组学策略。
